System, device, and method for determination of intraocular pressure

ABSTRACT

A system for determination of intraocular pressure includes: an intraocular pressure sensor; a light source illuminating the sensor with one or more wavelengths of light; and a detector that measures emitted light from the sensor. The sensor includes a substrate member, a spacer member, and a flexible membrane, which define a sealed cavity. The flexible membrane moves in response to intraocular pressure changes. A device for measuring intraocular pressure includes: the sensor; an anchoring member attached to the sensor for immobilizing the sensor in an eye; and a protective member attached to the anchoring member and covering the sensor to prevent contact between the flexible membrane and the eye. A method for determination of intraocular pressure includes: placing the sensor in an eye; illuminating, with a light source, the sensor with one or more wavelengths of light; and detecting, with a detector, a resultant light that contains information about intraocular pressure.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of prior application Ser. No.12/982,110, filed Dec. 30, 2010, which claims the benefit of U.S.Provisional Patent Application No. 61/291,131, filed Dec. 30, 2009, theentire disclosures of which are hereby incorporated by reference

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Subject matter described herein was made with U.S. Government supportunder contract number SBAHQ-08-I-0081 awarded by the Small BusinessAdministration. The government has certain rights in the describedsubject matter.

THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT

Not applicable.

INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC

Not applicable.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The present invention relates to systems, devices, and methods formeasuring pressure. More particularly, the present invention relates tosystems, devices, and methods for measuring intraocular pressure.

2. Background Art

Devices that measure intraocular pressure (TOP) by measuring theapplanation of the cornea are known in the art. Ophthalmologists usesuch devices to measure IOP in a physician's office. However, thesesingle-point measurements remain insufficient to fully manage eyedisease, particularly glaucoma. TOP peaks are missed in office hoursmeasurements, TOP fluctuations may be an independent risk factor, and amajority of glaucoma patients require changes to their topical and/orsurgical management approach after multiple TOP measurements on a singleday. Infrequent measurements also make it difficult to evaluatetreatment effectiveness and/or to assess patient compliance. However,more frequent, longer term tonometry is labor intensive, impractical,expensive, and often conducted only upon admission to an academichospital. Tonometers that can be used by the patient are know in theart, but these devices often cause discomfort, have proven difficult forpatients to repeatably administer, and have demonstrated unacceptableerror in clinical studies.

Implantable electronic devices for more frequent measurement ofintraocular pressure are known in the art. Readout of passive electronicsensors has proven problematic because inductively coupling to tinyreceivers in the sensor is difficult. Active sensors overcome thisproblem, but require implantable power sources or power storage systems,implanted integrated circuits, and large antennas. As a result, bothpassive and active systems have so far proven too large and complex,mostly irreversible, risky with regard to biocompatibility, and/or errorprone.

BRIEF SUMMARY OF THE INVENTION

According to one aspect of the invention, a system for determination ofintraocular pressure includes: an intraocular pressure sensor; a lightsource illuminating the intraocular pressure sensor with one or morewavelengths of light; and a detector that measures reflected and/oremitted light from the sensor. The intraocular pressure sensor includesa substrate member, a spacer member, and a flexible membrane. Thesubstrate member, the spacer member and the flexible membrane define asealed cavity. The flexible membrane moves and/or deforms in response tointraocular pressure changes.

In accordance with one implementation, the system further includes aprocessing device in communication with the detector. Then, the flexiblemembrane both transmits and reflects the one or more wavelengths oflight, the substrate member reflects the one or more wavelengths oflight transmitted by the flexible membrane, the light reflected by thesubstrate member interferes with light reflected from the flexiblemembrane to create an interference pattern, and the interference patterncorresponds to intraocular pressure. According to this implementation,the detector is an electronic imaging device capturing an image of theinterference pattern, and the processing device performs a phasecalculation on the image of the interference pattern to determine phaseangles of the interference pattern, and correlates the phase angles withintraocular pressure.

The processing device may further perform the phase calculation using anintegral transform and may calculate the phases at one or more spatialfrequencies corresponding to peaks in an absolute value of the integraltransform.

Also, the processing device may use the values of the spatialfrequencies corresponding to peaks in the absolute value of the integraltransform to correct for errors which arise from angular deviation of asensor normal from an optical axis of a readout system.

Still further, each wavelength emitted by the light source may have acoherence length longer than the twice the separation between theflexible membrane and the substrate member.

According to this implementation, the system may further include anoptical filter positioned between the intraocular pressure sensor and atleast one of the light source and the electronic imaging device. Theoptical filter provides an optical coherence length greater than twicethe distance from the flexible membrane to the substrate member.

The light source may be modulated in time to allow for lock-in detectionof the interference pattern.

Further, the light source may emit multiple wavelengths of light, eithersimultaneously or sequentially, and the dimensions of the flexiblemembrane may allow a phase change in the interference pattern of greaterthan 2π for at least one of the multiple wavelengths of light.

In accord with another implementation, the system further includes aprocessing device in communication with the detector, a coatingcontaining a fluorescent material coated on at least one of thesubstrate member and the flexible membrane, and a filter positionedbetween the intraocular pressure sensor and the detector. An externallight source excites the fluorescent material of the coating, thefluorescent material of the coating emits a light of a different secondwavelength, the emission of the light of the second wavelength being theresult of excitation of the fluorescent material, and the proximity ofthe flexible membrane to the substrate member modulates the intensity ofthe emitted light of a different second wavelength. The detector is alight intensity sensor. The filter allows only the second wavelength toreach the detector. Then, the processing device correlates the detectedintensity at the second wavelength with intraocular pressure.

According to another aspect of the invention, a device for measuringintraocular pressure includes: an intraocular pressure sensor includinga substrate member, a spacer member, and a flexible membrane, thesubstrate member, the spacer member and the flexible membrane defining asealed cavity wherein the flexible membrane moves and/or deforms inresponse to intraocular pressure changes; an anchoring member attachedto the intraocular pressure sensor for immobilizing the intraocularpressure sensor in an eye; and a protective member attached to theanchoring member and covering the intraocular pressure sensor to preventcontact between the flexible membrane and portions of the eye.

In accordance with one implementation, the anchoring member comprises aplate for insertion in a scleral pocket and for immobilizing the device,and an arm for entering an anterior chamber of the eye through a scleraltunnel. The plate may include holes for suturing the plate to the eye,and/or holes for assisting wound healing.

In accordance with another implementation, the anchoring member includesa pair of pincers to enclavate an iris of the eye.

In accordance with yet another implementation, the device furtherincludes a second intraocular pressure sensor having at least one of adifferent diameter, shape, membrane thickness, membrane material, andsubstrate material, such that the intraocular pressure sensor and thesecond intraocular pressure sensor provide at least one of redundantpressure measurement, failure detection, compensation for temperaturefluctuations in the eye, increased pressure measurement sensitivity, andincreased pressure measurement dynamic range.

The anchoring member and the protective member may be formed from abiocompatible material selected from a group consisting ofpolymethylmethacrylate, other acrylic plastics, silicone, otherbiocompatible plastics, biocompatible metals, and biocompatible metalalloys.

According to another aspect of the invention, an intraocular pressuresensor, includes: a substrate member; a spacer member; and a flexiblemembrane. The substrate member, the spacer member and the flexiblemembrane define a sealed cavity, and the flexible membrane moves and/orin response to intraocular pressure changes and the movement of theflexible membrane can be measured optically.

In accordance with one implementation, the sealed cavity has a pressurebelow one atmosphere.

In accordance with another implementation, light is both transmitted andreflected by the flexible membrane, and reflected by the substratemember, the light reflected by the substrate member interferes withlight reflected from the flexible membrane to create an interferencepattern, and the resulting interference pattern corresponds tointraocular pressure.

According to this implementation, material and dimensions of theflexible membrane may provide a number of periods in the interferencepattern to estimate phase within ±0.03 radians such that intraocularpressure can be measured with an accuracy of 1 mm Hg over a range of 610to 820 mmHg absolute pressure.

Also according to this implementation, the material and dimensions ofthe flexible membrane may prevent the membrane from contacting thebottom of the sealed cavity under pressures encountered in theintraocular environment.

Further in accord with this implementation, the materials and dimensionsof the flexible membrane may limit pressure measurement errors to lessthan 1 mm Hg in the presence of temperature fluctuations from 32° C. to36° C. typically encountered in the intraocular environment.

Still further in accord with this implementation, the material anddimensions of the flexible membrane and the thickness of the spacermember provide an interference pattern without using a light source thatrelies on laser action.

This implementation may further include a layer of additional materialcoated on the external side of the membrane, with the thickness andrefractive index of the additional material equalizing the reflectionfrom the flexible membrane and the substrate member.

Additionally, the material and dimensions of the membrane of thisimplementation may limit the phase change in the interference pattern toless than 2π over a range of 610 to 820 mmHg absolute pressure.

In accordance with another implementation, the intraocular pressuresensor includes a coating containing a fluorescent material, the coatingbeing coated on at least one of the substrate member and the flexiblemembrane. An external light source excites the fluorescent material ofthe coating, and the fluorescent material of the coating emits a lightof a different second wavelength, the emission of the light of thesecond wavelength being the result of excitation of the fluorescentmaterial. The proximity of the flexible membrane to the substrate membermodulates the intensity of the emitted light of a different secondwavelength and the detected intensity of the emitted light of thedifferent second wavelength is used to determine the pressure.

This implementation may further include a scattering medium coated on atleast one of the flexible membrane and the substrate member.

Also, in accordance with this implementation, the coating may furtherinclude a second fluorescent material, and the external light source mayfurther excite the second fluorescent material of the coating to emit alight of a different third wavelength. Then, the difference in detectedintensity of the emitted light at the second and third wavelengths maybe used to determine the pressure.

According to another aspect of the invention, a method for determinationof intraocular pressure includes placing an intraocular pressure sensorin an eye, the intraocular pressure sensor including a substrate member,a spacer member, and a flexible membrane, the substrate member, thespacer member and the flexible membrane defining a sealed cavity whereinthe flexible membrane moves and/or deforms in response to intraocularpressure changes. The method further includes illuminating, with a lightsource, the intraocular pressure sensor with one or more wavelengths oflight, and detecting, with a detector, a resultant light that containsinformation about intraocular pressure.

In accordance with one implementation, the flexible membrane bothtransmits and reflects the one or more wavelengths of light, thesubstrate member reflects the one or more wavelengths of lighttransmitted by the flexible membrane, and the light reflected by thesubstrate member interferes with light reflected from the flexiblemembrane to create an interference pattern. The interference patterncorresponds to intraocular pressure.

According to this implementation, detecting the resultant light includescapturing, with an electronic imaging device, an image of theinterference pattern, and the method further includes: performing aphase calculation on the image of the interference pattern to determinephase angles of the interference pattern; and correlating the phaseangles with intraocular pressure.

Then, this implementation may further include positioning an opticalfilter between the intraocular pressure sensor and at least one of thelight source and the electronic imaging device, the optical filterproviding an optical coherence length greater than twice the distancefrom the flexible membrane to the substrate member.

According to this implementation, the step of illuminating theintraocular pressure sensor includes modulating the light source in timeto allow for lock-in detection of the interference pattern by theelectronic imaging device.

In accordance with another implementation, the method further includescoating a layer containing fluorescent material on at least one of thesubstrate member and the flexible membrane. Illuminating the intraocularpressure sensor includes exciting the fluorescent material of thecoating with a light source such that the fluorescent material of thecoating emits a light of a different second wavelength, the emission ofthe light of the second wavelength being the result of excitation of thefluorescent material. Then, the proximity of the flexible membrane tothe substrate member modulates the intensity of the emitted light of adifferent second wavelength. Additionally, detecting the resultant lightincludes detecting an intensity of the emitted light of the differentsecond wavelength to determine the pressure.

In accordance with another implementation, placing the intraocularpressure sensor in the eye includes immobilizing the intraocularpressure sensor in the eye using an anchoring member attached to theintraocular pressure sensor. The anchoring member may include a plateand an arm, and the immobilizing the intraocular pressure sensor in theeye may further include: inserting the plate into a scleral pocket ofthe eye; and inserting the arm into an anterior chamber of the eyethrough a scleral tunnel. Also, immobilizing the intraocular pressuresensor in the eye may include suturing the plate to the eye using holesin the plate.

According to another aspect of the invention, a method for thedetermination of intraocular pressure uses an interference patternproduced by an intraocular pressure sensor. The intraocular pressuresensor includes a substrate member, a spacer member, and a flexiblemembrane. The substrate member, the spacer member and the flexiblemembrane define a sealed cavity; wherein the flexible membrane movesand/or deforms in response to intraocular pressure changes. The movementor deformation of the flexible membrane is measured optically. Lightfrom a light source, emitting one or more wavelengths of light eithersimultaneously or sequentially, is both transmitted and reflected by theflexible membrane, and reflected by the substrate member. The lightreflected by the substrate member interferes with light reflected fromthe flexible membrane to create an interference pattern. The methodincludes: performing, by a processing device, a phase calculation on theinterference pattern to determine phase angles of the interferencepattern, and correlating the phase angles with pressure. The phasecalculation may be performed using an integral transform and the phasesmay be calculated at one or more spatial frequencies corresponding topeaks in an absolute value of the integral transform. Additionally,values of the spatial frequencies corresponding to the peaks in theabsolute value of the integral transform may be used to correct forerrors which arise from angular deviation of a sensor normal from anoptical axis of a readout system.

Other features and advantages of the invention will be set forth in, orapparent from, the detailed description of exemplary embodiments of theinvention found below.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

These and other features, aspects, and advantages of the presentinvention will become better understood with regard to the followingdescription, appended claims, and accompanying drawings where:

FIG. 1 is a functional block diagram of an exemplary system fordetermination of intraocular pressure, according to the invention;

FIG. 2A and FIG. 2B are schematic cross-sectional views of exemplaryintraocular pressure sensors according to the invention;

FIG. 3A is a representation of an image of an exemplary interferencepattern;

FIG. 3B is a graph of an absolute value of an integral transform of theexemplary interference pattern of FIG. 3A;

FIG. 3C is a graph of an experimentally measured relationship betweenphase of an interference pattern and liquid pressure for an exemplaryintraocular pressure sensor;

FIG. 4A is another representation of an image of an exemplaryinterference pattern;

FIG. 4B is a graph of an absolute value of an integral transform of theexemplary interference pattern of FIG. 3A;

FIG. 5A is a schematic perspective view of an exemplary embodiment of adevice for measuring intraocular pressure according to the invention;

FIG. 5B is a schematic sectional view of an eye with the device of FIG.5A implanted therein;

FIG. 6A is a schematic plan view of another exemplary embodiment of adevice for measuring intraocular pressure according to the invention;

FIG. 6B is a schematic plan view of an eye with the device of FIG. 6Aimplanted therein;

FIG. 7A through FIG. 7D are schematic cross-sectional views of exemplaryintraocular pressure sensors according to the invention furthercomprising a coating containing a fluorescent material;

FIG. 8A and FIG. 8B are representations of interference patterns havinga phase change of 2π;

FIG. 9A and FIG. 9B are representations of interference patternsassociated with multiple, sequentially emitted wavelengths;

FIG. 9C and FIG. 9D are graphs of the absolute value of integraltransforms of the interference patterns of FIG. 9A and FIG. 9B,respectively;

FIG. 10A is a representation of an interference pattern associated withmultiple, simultaneously emitted wavelengths;

FIG. 10B is a graph of the absolute value of the integral transform ofthe interference pattern of FIG. 10A;

FIG. 11A through FIG. 11D are graphs showing a calculated ratio ofresultant light power to incident light power as a function ofmembrane-fluorescent coating separation;

FIG. 12 is a flow chart of an exemplary method for determination ofintraocular pressure according to the invention;

FIG. 13 is a flowchart of an exemplary method for the determination ofpressure from an interference pattern produced by an intraocularpressure sensor according to the invention; and

FIG. 14A and FIG. 14B are schematic perspectives view of furtherexemplary embodiments of a device for measuring intraocular pressureaccording to the invention.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS OF THE INVENTION

FIG. 1 shows an exemplary system 100 for frequent measurement ofintraocular pressure using an intraocular (i.e., inside or within aneye) pressure sensor 101 which, in use, would be implanted in an eye.The pressure is measured optically by the system 100 using a lightsource 102 to illuminate the intraocular pressure sensor 101 with one ormore wavelengths of incident light 103. A resultant light 113(comprising reflected light or a combination of reflected and emittedlight) is captured by a detector 106 and the signal from the detector106 is processed by a processing device 107 to determine the intraocularpressure.

The exemplary system 100 further comprises an objective lens 110, a beamsplitter 104, an illuminating lens 111, and a diffuser 112. Theobjective lens 110 performs at least one of the functions of collectinglight from the intraocular pressure sensor 101 and forming an image ofthe intraocular pressure sensor 101 on the detector 106. The beamsplitter 104 allows light from the source 102 to reach the intraocularpressure sensor 101 and the reflected light from the intraocularpressure sensor 101 to reach the detector 106. The illuminating lens 111and diffuser 112 provide well controlled, uniform illumination of theintraocular pressure sensor 101. The exemplary system 100 furthercomprises an atmospheric pressure sensor 109. The atmospheric pressuresensor 109 communicates with the processing device 107 to allowmeasurement of intraocular pressure with respect to atmosphericpressure. The atmospheric pressure sensor 109 can be an optical pressuresensor 101 as described here or one of several atmospheric pressuresensors known to those skilled in the art of pressure measurement.

FIG. 2A shows an exemplary intraocular pressure sensor 101 comprising asubstrate member 200, a spacer member 201, and a flexible membrane 202which define a sealed cavity 203. The flexible membrane 202 deflects inresponse to changes in intraocular pressure and these changes can bemeasured optically. The incident light 103 is both transmitted andreflected by the flexible membrane 202, and reflected by the substratemember 200. The light reflected by the substrate member 200 interfereseither constructively or destructively with light reflected from theflexible membrane 202 such that the resultant light 113 (FIG. 1)comprises an interference pattern 300, as shown in FIG. 3A.

The interference pattern 300 consists of bright and dark regions thatare referred to as interference fringes. The brightest and darkestlevels of the interference pattern 300 are shown as solid and dashedcontour lines in FIG. 3A. These interference fringes change positionwhen the flexible membrane 202 deflects in response to intraocularpressure changes as described in more detail below. Thus, theinterference pattern 300 corresponds to intraocular pressure.

The interference pattern 300 is captured using the detector 106 (FIG.1). In an embodiment the detector 106 is an electronic imaging devicesuch as a digital camera or photodetector array. In an embodiment, thedetector 106 communicates with a processing device 107 which performs aphase calculation on the image of the interference pattern 300 andcorrelates the calculated phase angles with intraocular pressure.

FIG. 3C shows the experimentally measured relationship between the phaseof the interference pattern 300 and liquid pressure for an intraocularpressure sensor 101 with a silicon substrate member 200, a siliconnitride flexible membrane 202, illuminated with a light emitting diodelight source 102 at a wavelength of similar to 800 nm.

As shown in FIG. 3B, the processing device 107 (FIG. 1) performs thephase calculation using an integral transform and calculates the phaseat one or more spatial frequencies corresponding to peaks 301 in anabsolute value of the integral transform 302. This calculation furtherallows for correction of pressure readings for angular deviationsbetween the optical axes of the detector 106 and the intraocularpressure sensor 101, as described in more detail below.

FIG. 4A shows an interference pattern 300 from a sensor 101 whoseoptical axis is tilted about the y-axis effectively compressing thepattern along the x-direction.

FIG. 4B, discussed below, shows the absolute value of an integraltransform 302 of the interference pattern 300.

In an embodiment each wavelength emitted by the light source 102(FIG. 1) has a coherence length longer than twice the separation betweenthe flexible membrane 202 and the substrate member 200 (FIGS. 2A and2B). Having a sufficiently long coherence length ensures that theinterference pattern 300 (FIG. 3A) can be clearly captured by thedetector 106 (FIG. 1). A shorter coherence length could be contemplated,but would reduce the visibility of the interference pattern 300 and thusreduce the signal to noise ratio of the detector 106 signal.

In an embodiment the light source 102 is a light emitting diode. A lightemitting diode is preferred because it emits a narrow range ofwavelengths such that the coherence length of the incident light 103 andresultant light 113 is between 1 μm and 1000 μm. This is appropriate forthe range of sealed cavity 203 thicknesses described in more detailbelow. Laser light sources also offer sufficiently long coherencelengths, but light emitting diodes offer greater eye safety.

In the exemplary system 100 shown in FIG. 1, an optical filter 105 ispositioned between the intraocular pressure sensor 101 and at least oneof the light source 102 and the detector 106. The optical filter 105increases the coherence length of at least one of the incident light 103and resultant light 113. The optical filter 105 is required if the lightsource 102 does not have an intrinsically long enough coherence length.In a preferred embodiment the filter is positioned immediately in frontof the detector so as to block other light not at the wavelength of theresultant light 113.

In a preferred embodiment the wavelengths of the incident light 103 arein the infrared spectral region so that the incident light 103 remainsinvisible to the patient.

In an embodiment, the light source 102 is modulated in time by amodulator 108 which also communicates with the processing device 107.The modulator modulates the light source by at least one of electricalor mechanical means or some combination of electrical and mechanicalmeans. The modulator 108 has a frequency such that many cycles arecontained in a single intraocular pressure measurement. The modulatingsignal can be any of several periodic signals, such as a sine wave orsquare wave, that are familiar to those skilled in the art. The signalfrom the modulator 108 is also routed to the processing device 107 whereit is combined with the signal from the detector 106 for phase-locked(or “lock-in”) detection, a technique well known to those skilled in theart of low-level signal measurements. This detection method reducesnoise that could be introduced by light sources, for example roomlights, other than the resultant light 113.

In an embodiment the light source 102 emits multiple wavelengths oflight in order to improve at least one of the precision and dynamicrange of the pressure measurement. This is particularly important fordesigns of the intraocular pressure sensor 101 in which the deflectionof the flexible membrane 202 yields a phase change of greater than 2π.

FIG. 8A and FIG. 8B show interference patterns 300 having a phase changeof 2π.

A single wavelength measurement of a single intraocular pressure sensor101 (FIG. 1) would exhibit pressure ambiguities if the phase changes bymore than 2π, as described in more detail below.

FIG. 9A and FIG. 9B show interference patterns 300 associated with eachwavelength captured by the detector 106 in an embodiment where multiplewavelengths are emitted sequentially. The processing device 107 (FIG. 1)calculates the phase angle of each interference pattern 300 at spatialfrequencies corresponding to the illuminating wavelengths as describedin more detail below.

As shown in FIG. 10A, in an alternative embodiment the light source 102emits the multiple wavelengths simultaneously, and a more complexinterference pattern 300 is generated. The processing device 107 nowcalculate the phase angles from a single interference pattern 300 but atmultiple spatial frequencies, each spatial frequency corresponding to adifferent wavelength, as described in more detail below.

In yet another embodiment, as shown in FIG. 7A and FIG. 7B respectively,the intraocular pressure sensor 101 further comprises a coating 700containing a fluorescent material, the coating 700 being coated on atleast one of the substrate member 200 and the flexible membrane 202. Asused herein, a fluorescent material is a material which absorbselectromagnetic energy of a specific first wavelength and re-emitsenergy at different (but equally specific) additional wavelengths. Afluorophor is a component, such as a fluorescent dye molecule, of afluorescent material which absorbs electromagnetic energy of a specificfirst wavelength and re-emits energy at different (but equally specific)second wavelength. A fluorescent material may contain one or morefluorophors. The incident light 103 excites the fluorescent material ofthe coating 700, and the fluorescent material of the coating 700 emitslight of a different second wavelength, the emission of the light of thesecond wavelength being the result of excitation of the fluorescentmaterial. After passing back through the flexible membrane, and perhapsbeing further modulated, the emitted light of a different secondwavelength becomes the resultant light 113.

In an embodiment, the proximity of the flexible membrane 202 to thesubstrate member 200 modulates the intensity of the resultant light 113.In an embodiment the intensity of the resultant light 113 from theintraocular pressure sensor 101 is modulated based on several phenomenadescribed in more detail below. In an embodiment the detector 106 is oneor more light intensity sensors. The light intensity sensors may be atleast one of photodiodes or photomultipler tubes. The signal from thedetector 106 corresponds to intraocular pressure, and the processingdevice 107 processes the signal to determine intraocular pressure. In anembodiment the optical filter 105 is placed between the intraocularpressure sensor 101 and the detector 106 such that only the secondwavelength in the resultant light 113 reaches the detector 106.

Movement of the intraocular pressure sensor 101 with respect to theassembly containing the detector 106 must be considered. The assemblymay be at least one of a handheld unit, a head mounted unit, and an eyeglass mounted unit. The assembly may or may not contain the light source102.

In an embodiment relative motion is limited by providing a target atwhich the patient gazes while the pressure measurement is acquired. Thetarget can be real structure or a virtual image created using opticswithin the assembly. Those skilled in the art have found that angularmotions are limited to less than 0.2 degrees during visual fixation.

In an embodiment an eye cup can be added to the assembly containing thedetector 106. The eye cup contacts the face during the pressuremeasurement in order to physically limit movement of the intraocularpressure sensor 101 with respect to the detector 106.

In an embodiment, at least one of autofocus mechanisms or imagestabilization mechanisms, familiar to those skilled in the art, areadded to the assembly to minimize the movement of the sensor 101 imageand the detector 106.

In an embodiment the detector 106 is an electronic image sensor with aframe rate in excess of 100 frames per second. The frame rate allowsimages to be captured during times when the sensor is in focus andwithin the field of view of the electronic image sensor.

The processing device 107 is preferably at least one of a dedicatedelectronic circuit, a microprocessor, a digital signal processor, or aprogrammable logic device. The processing device 107 may be eitherinternal or external to the assembly containing the detector 106. Theprocessing device is connected to the detector by at least one of aphysical electrical connection, a wireless connection, or a networkconnection all of which are familiar to those skilled in the art.

FIG. 5A shows a device for measuring intraocular pressure comprising anintraocular pressure sensor 101 and an anchoring member 500. Theanchoring member comprises a protective member 501, a plate 502, and anarm 503.

FIG. 5B shows an eye 505 with the device implanted through the sclera508 such that the intraocular pressure sensor 101 is located in theanterior chamber 506 and is visible through the cornea 507. Theprotective member 501 prevents the intraocular pressure sensor 101 fromcontacting the cornea 507 in case of movement of the sensor toward thecornea 507. The dimensions of the plate 502 are chosen so that it can befixed in a scleral pocket. Although other dimensions could becontemplated, a long dimension of 1 to 5 mm and a short dimension of 1to 3 mm are appropriate.

In one embodiment the plate 502 contains holes 504 for suturing theanchoring member 500 to the sclera 508. Although other dimensions couldbe contemplated, the diameter of the holes should be greater thanapproximately 50 μm to permit an atraumatic needle and suture to pass.

In an embodiment the plate 502 contains holes 504 to assist in woundhealing. In this case the sclera 508 closes through the holes to promoteboth healing and immobilization of the device. The dimensions of the arm503 are such that the arm can extend through a scleral tunnel placingthe intraocular pressure sensor 101 in a position within the anteriorchamber 506 such that the intraocular pressure sensor 101 is visiblethrough the cornea 507. Other dimensions could be contemplated, but anarm width of 1 to 2 mm and an arm length of 2 to 7 mm are acceptable.

In an embodiment shown in FIG. 6A and FIG. 6B, the anchor member 500comprises a pair of 600 on at least one end such that it can be attachedto the iris 601 rather than fixed in the sclera 508. In this embodimentthe anchor member 500 along with the attached intraocular pressuresensor 101 is inserted into the anterior chamber 506 and placed on theiris 601 such that it does not block the pupil 602. The tissue of theiris is enclavated by the pincers 600 to immobilize the anchor member500 in the eye 505.

In an embodiment shown in FIG. 14A two or more intraocular pressuresensors 101 can be included in the same device. This provides redundantpressure measurements that increase confidence in the pressure reportedby the intraocular pressure measurement system 100. In addition, if onesensor fails, the deviation in readings between the first sensor and anyadditional sensors will serve as an indication of the failure.

In an embodiment shown in FIG. 14B, the second intraocular pressuresensor 101 has at least one of a different diameter, shape, flexiblemembrane 202 thickness, flexible membrane 202 material, and substratemember 200 material. The two or more pressure sensors 101 provide atleast one of redundant pressure measurement, failure detection,compensation for temperature fluctuations in the eye, increased pressuremeasurement precision, increased pressure measurement dynamic range. Inthis embodiment, the flexible membrane 202 deflection due to temperaturechanges and the flexible membrane 202 deflection due to pressure changesare different for the two different sensors 101. Thus, the pressure andtemperature can be separately measured by solving a set of simultaneousequations of the form:(θ₁−θ₀₁)=S _(1T)(T−T ₀)+S _(1P)(P−P ₀)(θ₂−θ₀₂)=S _(2T)(T−T ₀)+S _(2P)(P−P ₀)′where θ₁ and θ₂ are the phases for the interference pattern 300 or theintensities associated with the fluorescence for the first and secondsensor respectively. θ₀₁ and θ₀₂ are known reference phases for theinterference pattern 300 or known reference intensities associated withthe fluorescence for the first and second sensor respectively. S_(1T)and S_(2T) are the sensitivities of the first and second sensor tochanges in temperature, for example in radians/° C. or intensity/° C.,S_(1P) and S_(2P) are the sensitivities of the first and second sensorto changes in pressure, for example in radians/mmHg or intensity/mmHg, Tis the temperature and T₀ is a known reference temperature, and P is thepressure and P₀ is a known reference pressure.

An exemplary device with two intraocular pressure sensors 101 includesone sensor with diameter similar to 300 um and another with diametersimilar to 400 um. The flexible membrane 202 thickness is similar to 1.5μm for both sensors. The sensitivities of the two intraocular pressuresensors 101 to changes in pressure are similar to 0.020 radians/mmHg and0.037 radians/mmHg respectively for intraocular pressure ranges from 730mmHg to 780 mmHg (10 to 50 mmHg above atmospheric pressure at sealevel). The sensitivity of the two sensors 101 to changes in temperatureare similar to 0.014 radians/° C. and 0.023 radians/° C. respectively.Thus, the interference patterns 300 from the two sensors allowdifferentiation between changes in pressure and temperature.

In an embodiment, the flexible membrane 202 deflection due to pressurechanges is different for two sensors 101. Pressure is determined bymeasuring the phase angles of the interference patterns 300 from bothsensors. If the phase change for at least one of the interferencepatterns 300 exceeds 2n the pressure can still be determined uniquelybased on the phase of the other interference pattern. In addition, ifthe desired dynamic range is kept constant, the use of two sensors withhigher sensitivity, but at least one with total phase change greaterthan 2π, can improve sensitivity and thus sensing precision andaccuracy.

An exemplary device with two intraocular pressure sensors 101 includesone sensor 101 with diameter similar to 300 um and flexible membranethickness similar to 1.5 μm and another sensor 101 with flexiblemembrane 202 diameter similar to 600 um and flexible membrane 202thickness similar to 200 nm. The sensitivity of the two sensors 101 tochanges in pressure are 0.020 radians/mmHg and 0.074 radians/mmHgrespectively from 730 mmHg to 780 mmHg. For a desired dynamic range of610 to 820 mmHg the first sensor undergoes a total phase change ofsimilar to 4.8 radians and the second sensor undergoes a total phasechange similar to 16 radians. In this exemplary case the first sensor101 provides a coarse measurement of pressure with no ambiguity over theentire pressure range, and the second sensor 101 provides a moresensitive measurement of pressure with ambiguity among several pressureswithin the range. However, the first sensor 101 removes this ambiguity.Using two sensors 101 allows intraocular pressure to be measured withgreater sensitivity without sacrificing dynamic range. Other sensordesigns can be contemplated that would expand dynamic range withoutsacrificing sensitivity.

The anchoring member 500 is formed from materials that are biocompatiblewhen implanted in the eye. Possible materials includepolymethylmethacrylate, other acrylic plastics, and silicone. Thesematerials are commonly used for intralocular lenses. In addition,biocompatible metals and metal alloys containing elements such as goldor titanium are possible materials for the anchoring member.

As discussed above, FIG. 2A shows an intraocular pressure sensor 101comprising a substrate member 200, a spacer member 201, a flexiblemembrane 202 which define a sealed cavity 203. The flexible membrane 202deflects in response in response to intraocular pressure changes and thedeflection of the flexible membrane 202 can be measured optically. Thesubstrate member 200 consists of at least one biocompatible metal,semiconductor, or insulator material. The spacer member 201 consists ofat least one biocompatible metal, semiconductor, or insulator material.The spacer member 201 prevents fluid from penetrating into the sealedcavity 203. In an embodiment the spacer member 200 material is at leastone of silicon, silicon nitride, and silicon dioxide. The spacer member201 can be formed by one of several processes familiar to those skilledin the art of microfabrication including at least one of etching ordeposition.

In a preferred embodiment the sealed cavity 203 has a pressure below oneatmosphere. The reduced cavity pressure reduces the temperaturesensitivity of the device because expansion or contraction of the gasinside the cavity will not create large changes in the separation of theflexible membrane 202 from the substrate member 200. A sealed cavity 203with reduced pressure can be formed by one of several processes familiarto those skilled in the art of microfabrication including at least oneof vacuum contact bonding, vacuum anodic bonding, vacuum adhesivebonding, thermal annealing, etching through release holes and lowpressure chemical vapor deposition sealing of these holes, and getteringof residual gas in the cavity.

The flexible membrane 202 is substantially impermeable to gas or liquidin order to maintain the integrity of the sealed cavity 203 over thelife of the intraocular pressure sensor 101. In a preferred embodiment,the flexible membrane 202 consists of silicon nitride. Silicon nitrideis one of the best known moisture and gas barriers, with no measurablepermeation, even at 1100° C.

In an embodiment, an incident light 103 (FIG. 1) strikes the intraocularpressure sensor 101 and is partially reflected and partially transmittedby the flexible membrane 202. The transmitted light is partiallyreflected by the substrate member 200. Reflected light from the flexiblemembrane 202 and the substrate member 200 combine to form a resultantlight 113. Light reflected by the substrate member 200 interferes eitherconstructively or destructively with light reflected from the flexiblemembrane 202 to create an interference pattern 300 (FIG. 3). Theresulting interference pattern 300 corresponds to intraocular pressure,as described in more detail below.

The substrate member 200 consists of a material with the correct opticalproperties and surface finish to at least partially reflect light at theillumination wavelength. The substrate member 200 material is chosenfrom a group including at least one of biocompatible metals,semiconductors, or insulators. In an embodiment, the substrate member200 is made of polished silicon which is partially reflective throughoutthe visible and near-infrared spectral region. In another embodiment thesubstrate member 200 is made from a glass, plastic, semiconductor, oroxide material. In another embodiment, the substrate member 200 materialis optically transparent for visible wavelengths but is reflective atinfrared wavelengths. In another embodiment, the substrate member 200 iscoated with another layer of material or multiple layers of materials torender it reflective in the infrared. In this way the sensor istransparent in the visible spectral region but reflective in theinfrared region to improve the aesthetics of the sensor.

The flexible membrane 202 consists of a material with the correctoptical properties and correct thickness to partially, but not entirely,reflect an incident light 103. In this way an optical cavity is formedand an optical interference pattern 300 is generated. In one embodimenta flexible membrane 202 consists of at least one of silicon, siliconnitride, and silicon dioxide. A flexible membrane 202 can be formed byone of several processes familiar to those skilled in the art ofmicrofabrication including at least one of implantation, oxidation,physical vapor deposition, chemical vapor deposition, and etching.

The interference pattern 300 consists of bright and dark regions thatare often referred to as interference fringes. These interferencefringes change position when the flexible membrane 202 deflects withrespect to the substrate member. The separation of these rings dependson the curvature of the flexible membrane 202 surface. If the separationof the flexible membrane 202 and the substrate member 200 changes thenthe rings shift in radial position. If the curvature of the flexiblemembrane 202 surface changes then the spacing of the rings changes. Thevisibility, the difference in intensity between brightest and darkestpoints divided by sum of the intensities between the brightest anddarkest points, of the rings at the detector 106 is determined by theseparation of the substrate member 200 and the flexible membrane 202 andthe coherence length of the resultant light 113.

The materials and dimensions of the flexible membrane allow a number ofperiods in the interference pattern 300 and sufficient deflection todetect clinically important changes in intraocular pressure. In it knownthat intraocular pressure changes of 1 mmHg have clinical significancein managing glaucoma. In an exemplary sensor the flexible membrane 202is circular with a diameter of 300 μm and a thickness of 1.5 The sealedcavity 203 contains a vacuum. The spacer member is greater than 5 μmthick but less than twice the coherence length of the incident light103. At 820 mmHg absolute pressure (60 mmHg above atmospheric pressureat sea level) the flexible membrane 202 deflects similar to 3.6 μm atits central point. This gives rise to 9 periods in the interferencepattern 300 when illuminated with an incident light 103 of 800 nmwavelength. To measure intraocular pressure from 10 to 60 mmHg withrespect to atmospheric pressure at elevations from sea level to 2000 mthe sensor 101 measures absolute pressures from 610 mmHg to 820 mmHg.For a light source 102 emitting a single wavelength, the interferencepattern 300 is limited to a maximum phase change of 2n over thispressure range. Thus the intraocular pressure measurement system 100must measure the phase to ±0.03 radians to maintain an accuracy of 1mmHg. With a signal to noise ratio as low as 1, the standard deviationof the phase estimate is similar to 0.01 radians when the signal iscaptured using only 200×200 pixel electronic image sensor. We definesignal to noise ratio as the square of the amplitude of the interferencepattern 300 modulation divided by the variance of an additive Gaussiannoise. This noise level is much larger and the image resolution muchsmaller than what would be typically encountered in practice, thus theprecision of the phase measurement is sufficient to detect clinicallyrelevant changes in intraocular pressure.

The material and dimensions of the flexible membrane 202 and thedimensions of the spacer layer 201 prevent the membrane 202 fromcontacting the bottom of the sealed cavity 203 under pressuresencountered in the intraocular environment. In an exemplary sensor 101the flexible membrane 202 consists of non-stoichiometric, low-stresssilicon nitride with an elastic modulus similar to 200 GPa and a Poissonratio similar to 0.27. The flexible membrane 202 diameter is 300 μm andthe flexible membrane 202 thickness is 1.5 The sealed cavity 203contains a vacuum. At 820 mmHg absolute pressure (60 mmHg aboveatmospheric pressure at sea level) the flexible membrane 202 deflectssimilar to 3.6 μm toward the substrate member 200 at its center. If thespacer member 201 is greater than 3.6 μm thick then the flexiblemembrane 202 will not contact the substrate member 200. Other dimensionsand materials could be contemplated that also prevent contact betweenthe flexible membrane 202 and the substrate member 200.

In a preferred embodiment an intraocular pressure sensor 101 limitspressure measurement errors to 1 mmHg in the presence of temperaturefluctuations from 32° to 36°. This range represents the approximaterange of corneal temperature variation for ambient temperatures rangingfrom 18° C. to 27° C. It is known that variations in corneal temperaturerepresent an upper bound on variations in the anterior chamber. In anexemplary sensor 101 the flexible membrane 202 consists ofnon-stoichiometric, low-stress silicon nitride with an elastic modulussimilar to 200 GPa, a Poisson ratio similar to 0.27, and a coefficientof thermal expansion similar to 2.3×10⁻⁶/° C. One skilled in the art ofmicrofabrication will understand that the mechanical properties ofsilicon nitride thin films can vary depending on deposition conditionsand stoichiometry, and that other mechanical properties could becontemplated that would yield similar behavior. The flexible membrane202 diameter is 500 μm and the flexible membrane 202 thickness is 0.5The sealed cavity 203 contains a vacuum. The substrate member 200 andthe spacer member 201 consist of silicon with a coefficient of thermalexpansion of 2.6×10⁻⁶/° C. The spacer member is greater than 11 μmthick. The illumination wavelength is 800 nm. At a normal intraocularpressure of 15 mmHg (735 mmHg absolute pressure at sea level) thepressure measurement error with change in temperature is similar to 0.12mmHg/° C. This restricts the measurement error to less than ±0.25 mmHgunder the anterior chamber temperature fluctuations described above. Inan embodiment, the intraocular pressure measurement system 100 indicatesthe pressure measurement is potentially erroneous if extreme ambienttemperatures are detected. In an embodiment, the pressure sensor 101 iscalibrated for extreme ambient temperatures. Other dimensions andmaterials could be contemplated that also reduce temperature dependenceto acceptable levels.

In a preferred embodiment an intraocular pressure sensor 101 has aspacer member 201 with a thickness that provides an interference pattern300 without using a light source that relies on laser action. Thecoherence length of the incident light 103 must be longer than twice thethickness of the sealed cavity 203. The spacer member 201 has athickness that ensures the separation of the flexible membrane 202 andthe substrate member 200 is less than half the coherence length of theincident light 103. Laser light sources typically have coherence lengthsof greater than 1 mm. However, eye safety concerns when using lasersindicate that a light emitting diode light source is preferred. Lightemitting diodes have coherence lengths ranging from approximately 1 μmto 1000 μm. In an embodiment, an optical filter 105 is used to furtherincrease the coherence length of at least one of the incident light 103or the resultant light 113. In an exemplary sensor the spacer member isless than 50 μm thick so that the separation between the flexiblemembrane 202 and the substrate member 200 does not exceed 50 um and thusan incident light 103 with a coherence length of less than 25 μm can beused to form the interference pattern 300. For an infrared light source102 with a center wavelength of 800 nm this corresponds to a spectralbandwidth of approximately 25 nm. Other dimensions could be contemplatedthat also allow light sources 102 not employing laser action to be used.One skilled in the art of interferometry will understand that there aresubtle differences in definition of coherence length and spectralbandwidth depending on the spectral shape of the light, the criterionfor bandwidth, and the criterion for coherence. As such, one skilled inthe art will understand that the numbers given are representative andthat other criteria for coherence length could be conceived.

In one embodiment, shown in FIG. 2B, the intraocular pressure sensor 101further comprises one or more layers 204 of additional material coatedon the external side of the flexible membrane 202. This additionalmaterial has refractive index and thickness such that reflection fromthe membrane 202 is substantially equal to the reflection from thesubstrate member 200. Equalizing the reflection from the membrane 202and substrate member 200 provides the greatest interference pattern 300visibility, where visibility is defined as the ratio of the differencesin the maximum and minimum intensity in the interference pattern 300 tothe sum of the maximum and minimum intensity. As a result, the signal tonoise ratio of the captured interference pattern 300 will be maximizedif all other conditions are equal. It is important to note that forcertain combinations of flexible membrane 202 thickness and refractiveindex the additional layer 204 is unnecessary because the reflection isintrinsically balanced. However, the thickness of the flexible membrane202 is often determined by the pressure range and sensitivity required,and cannot be freely adjusted based on optical considerations. In anexemplary intraocular pressure sensor 101 the substrate member 200 issilicon with refractive index similar to 3.7, the flexible membrane 202is low stress silicon nitride with refractive index similar to 2.2 andthickness similar 350 nm, the additional layer 204 is one of severalpoly(p-xylylene) polymers with a refractive index similar to 1.6 and athickness similar to 150 nm, and the illumination wavelength is similarto 800 nm. In this example the interference pattern 300 visibilityimproves from 0.48 without the additional layer 204 to 0.75 with theadditional layer 204 in place. Other materials with different refractiveindices and thicknesses could be conceived to achieve a similarimprovement.

In the case of a single intraocular pressure sensor 101 illuminated by asingle wavelength of light, the phase change of the interference pattern300 is restricted to the less than 2n over the range of pressures to bemeasured. In an exemplary sensor the flexible membrane diameter is 300μm and the flexible membrane thickness is 1.5 The wavelength ofillumination is 800 nm. Over a range of absolute pressures from 610 mmHgto 820 mmHg the sensor's 101 sensitivity is similar to 0.02 radians/mmHgand the interference pattern 300 undergoes a phase change of less than2π. As a result, there is no ambiguity in the pressure measurementsbetween 610 mmHg and 820 mmHg. Other dimensions and materials for theflexible membrane 202 could be contemplated that also restrict the phasechange to 2n over a desired pressure range.

In the embodiment shown in FIG. 7A, the intraocular pressure sensor 101further comprises a coating 700 containing a fluorescent material on thesubstrate member 200. A light source 102 excites the fluorescentmaterial of the coating 700 and the fluorescent material of the coatingemits a light of a different second wavelength. The proximity of theflexible membrane 202 to the substrate member 200 modulates theintensity of the emitted light of a different second wavelength and thedetected intensity of the emitted light of the different secondwavelength is used to determine the pressure. The coating 700 can be anymaterial that is intrinsically fluorescent or that has been dyed with afluorescent component. An example coating could be a polymer, such aspoly-methyl methacrylate (PMMA), dyed with fluoresecent molecules, suchas the near-infrared polymethine dyes. In an embodiment both the polymerand the dye are be transparent in the visible part of the spectrum foraesthetic reasons. In an embodiment, both excitation and emissionwavelengths are in the near infrared to prevent the patient from seeingthe incident light 103 or resultant light 113 while the pressure isbeing measured. In another embodiment shown in FIG. 7B, the intraocularpressure sensor 101 further comprises a coating 700 containing afluorescent material on the flexible membrane 202.

The intensity of the resultant light 113 from the pressure sensor 101 ismodulated based on several phenomena. First the intensity of incidentlight 103 that reaches the fluorescent coating 700 is modulated. Thisoccurs because of wave optical effects typically described in terms of(1) interference of optical reflections from the membrane surfaces, thefluorescent material surfaces, and the substrate and (2) opticalnear-field and evanescent coupling across the sealed cavity when theseparation of the membrane and substrate are on the order of thewavelength of light. When light is transmitted through two or morepartially reflective surfaces it can interfere constructively anddestructively depending on the separation of the surfaces. As a result,the transmitted power in the resultant light 103 depends on theseparation of the surfaces. In the pressure sensor 101 there are atleast four partially reflected surfaces: the two surfaces of theflexible membrane 202; the interface of the fluorescent coating 700 withthe sealed cavity 203; and the interface of the substrate member 200with the fluorescent coating 700. First, the transmission of incidentlight 103 to the fluorescent coating 700 is modulated by the separationbetween the flexible membrane 203, which is partially reflective, andthe fluorescent coating 700 on the substrate member 200. As thetransmitted power at the excitation wavelength changes, the lightemission from the fluorescent coating 700 is modulated as well.

The same effects that modulate the intensity of incident light 103reaching the fluorescent coating 700 also modulates the resultant light113. In addition, a significant fraction of the light emitted by thefluorescent coating 700 is reflected back into the material by totalinternal reflection. If the refractive index of the fluorescent coating700 is greater than the underlying substrate member 200, then this lightis completely trapped in the fluorescent layer. In either case, theevanescent electric field from the internally reflected light extends ashort distance beyond the interface between the fluorescent coating 700and the sealed cavity 203. If the flexible membrane 203 is sufficientlyclose to the fluorescent coating 700 (separation similar to wavelength)then light that would otherwise be totally internally reflected in thefluorescent coating 700 will couple into the flexible membrane 202. Thestrength of this coupling is strongly dependent on the separation of thetwo layers; thus, a change in pressure that deflects the flexiblemembrane 202, alters the fluorescent membrane 202-fluorescent coating700 separation, and the light emission. Moreover, light will be trappedin the flexible membrane 202 by total internal reflection.

In an exemplary pressure sensor 101, a substrate member 200 is coatedwith a fluorescent coating 700 with real refractive index 1.7 and thatis sufficiently thick and absorbing to absorb all of the excitationlight. A flexible membrane 202 is separated from the fluorescent coating202 by a sealed cavity 203 containing vacuum. The pressure sensor 101 isexcited with the incident light 113 at wavelength of 770 nm in the nearinfrared and the fluorescent coating 700 emits at 800 nm. Forexplanatory purposes, the incident light 103 is normally incident,unpolarized, and collimated, and the fluorescence yield (or quantumefficiency) is 1. The resultant light 113 emitted from the fluorescentcoating 700 is unpolarized and has a diffuse (Lambertian) distribution.

FIG. 11A shows a calculated ratio of resultant light 113 power toincident light 103 power as a function of membrane 202-fluorescentcoating 700 separation. This ratio is a direct measure of membrane 202deflection and thus a measure of pressure.

The pressure sensor 101 need not operate with collimated incident light103 or with normally incident light 103. However, the output of thepressure sensor 101 is dependent on the angle of illumination, ϕ.

FIG. 11B shows a calculated ratio of resultant light 113 power toincident light 103 power as a function of membrane 202-fluorescentcoating 700 separation with an illumination angle of 10 degrees fromnormal. The relationship is different and this angle dependence musteither be calibrated out of the pressure reading or eliminated by a moresophisticated sensor design described in more detail below.

In an embodiment shown in FIG. 7C, the flexible membrane 203 is alsocoated with a scattering medium 701 on the side of the membrane externalto the sealed cavity 203 to enhance light emission from the sensor 101and minimize illumination angle dependence, as further described below.An example of such a scattering medium is polytetrafluoroethylene.Modulation of the incident light 103 reaching the fluorescent layer andmodulation of the resultant light 113 exiting the sensor are bothgoverned by the phenomena described above. The scattering medium 701serves two purposes. First the scattering medium 701 randomizes theangle of incident light 103 to reduce output dependence on the angle ofillumination. Secondly, the scattering medium 701 serves to extractlight from the flexible membrane 202 and the fluorescent coating 700that would otherwise be trapped by total internal reflection. This bothincreases the total amount of light emitted by the sensor and alters therelationship between the amount of resultant light 113 and the flexiblemembrane 202—fluorescent coating 700 gap.

In an alternative embodiment, shown in FIG. 7D, the scattering medium701 is placed on the surface of the flexible membrane 202 inside thesealed cavity 203. This configuration can improve light extraction fromthe fluorescent material because the scattering medium 701 is in aregion of greater evanescent electric field strength.

In an exemplary sensor a scattering medium 701 is coated on the flexiblemembrane 202 surface external to the sealed cavity 203. Both incidentlight 103 and emitted light are diffusely (Lambertian) scattered at themembrane surface. As a result, the ratio of incident light 103 power toresultant light 113 power is no longer dependent on angle ofillumination. However, the angle of illumination will affect the totalinput power coupled into to the sensor.

FIG. 11C plots the calculated ratio of resultant light 113 power toincident light 103 power as a function of flexible membrane202-fluorescent coating 700 separation with the scattering medium 701 onthe external side of the flexible membrane 202. This relationship isindependent of illumination angle.

In an embodiment, the fluorescent coating 700 is placed in the flexiblemembrane 202, rather than on the substrate member 200, as shown in FIG.7B. This embodiment is governed by the same phenomena; however,interference effects, near field effects, and evanescent coupling areall modified by the position of the fluorescent coating 700 in relationto the other sensor components. Specifically, light is trapped in thecombined structure of the fluorescent coating 700 and the flexiblemembrane 202, and is evanescently coupled to the substrate member 200depending on the fluorescent coating 700—substrate member 200separation.

In another embodiment of the exemplary intraocular pressure sensor 101,two different fluorophors are contained in the fluorescent coating 700,and the two fluorophors emit light at two different wavelengths. Thedetector 106 measures the ratio of optical power at the two differentwavelengths. In an embodiment the detector comprises a dichroic beamsplitter and two light sensors. Each light sensor detects only onewavelength. In another embodiment, the detector comprises a beamsplitter, two optical filters, and two light sensors. Again, each lightsensor detects only one wavelength. By measuring the difference indetected optical power between the two sensors, the pressure measurementsystem 101 can compensate for different excitation and emissionefficiencies that occur when the eye moves relative to the light source102 and the detector 106 during or between measurements.

In an exemplary sensor 101 the fluorescent coating 700 emits at twowavelengths, 800 nm and 900 nm. When both fluorophors are excited, theratio of the detected intensity between the two wavelengths correspondsto intraocular pressure. In this way we need not know the excitationpower for any given measurements.

FIG. 11D plots the ratio of light detected at 800 nm to that detected at900 nm as a function of the flexible membrane 202—fluorescent coating700 separation.

As shown in FIG. 12, an exemplary method 1200 for determination ofintraocular pressure, includes the steps of: S1202 placing anintraocular pressure sensor 101 (FIG. 1) in an eye (e.g., eye 505 ofFIG. 5B), the intraocular pressure sensor 101 including a substratemember 200, a spacer member 201, and a flexible membrane 202, thesubstrate member 200, the spacer member 201 and the flexible membrane202 defining a sealed cavity 203 wherein the flexible membrane 202 movesand/or deforms in response to intraocular pressure changes; S1204illuminating, with a light source 102, the intraocular pressure sensor101 with one or more wavelengths of light; and S1206 detecting, with adetector, a resultant light that contains information about intraocularpressure.

In an embodiment, the flexible membrane 202 (FIG. 2) both transmits andreflects the one or more wavelengths of light, the substrate member 200reflects the one or more wavelengths of light transmitted by theflexible membrane 202, the light reflected by the substrate member 200interferes with light reflected from the flexible membrane 202 to createan interference pattern 300, and the interference pattern 300corresponds to intraocular pressure.

In an embodiment, the step S1206 detecting the resultant light includescapturing, with an electronic imaging device, an image of theinterference pattern 300, and the method further comprises a step S1208performing a phase calculation on the image of the interference pattern300 to determine phase angles of the interference pattern 300; and astep S1210 correlating the phase angles with intraocular pressure.

In an embodiment, the method further comprises a step S1212 positioningan optical filter 105 between the intraocular pressure sensor 101 and atleast one of the light source 102 and the electronic imaging device, theoptical filter 105 providing an optical coherence length greater thantwice the distance from the flexible membrane 202 to the substratemember 200.

In an embodiment, the step of S1204 illuminating the intraocularpressure sensor includes modulating the light source 102 in time toallow for lock-in detection of the interference pattern 300 by theelectronic imaging device.

In an embodiment, the method further comprises a step S1214 coating acoating 700 containing fluorescent material on at least one of thesubstrate member 200 and the flexible membrane 202, wherein the stepS1204, illuminating the intraocular pressure sensor, includes excitingthe fluorescent material of the coating 700 with a light source 102 suchthat the fluorescent material of the coating 700 emits a light of adifferent second wavelength, the emission of the light of the secondwavelength being the result of excitation of the fluorescent material,wherein the proximity of the flexible membrane 202 to the substratemember 200 modulates the intensity of the resultant light 113 of adifferent second wavelength, and wherein the step S1206 detecting theresultant light, includes detecting an intensity of the resultant light113 of the different second wavelength to determine the pressure.

In an embodiment, the step S1202, placing the intraocular pressuresensor in an eye, further includes immobilizing the intraocular pressuresensor 101 in the eye 505 using an anchoring member 500 attached to theintraocular pressure sensor 101.

In an embodiment, the anchoring member 500 comprises a plate 502 and anarm 503, and immobilizing the intraocular pressure sensor 101 furtherincludes inserting the plate 502 into a scleral pocket of the eye 505;and inserting the arm 503 into an anterior chamber 506 of the eyethrough a scleral tunnel.

In an embodiment, immobilizing the intraocular pressure sensor in theeye further includes suturing the plate 502 to the eye using holes 504in the plate 502.

As shown in FIG. 13, an exemplary method 1300 for the determination ofpressure from an interference pattern 300 produced by an intraocularpressure sensor 101 comprising a substrate member 200; a spacer member201; and a flexible membrane 202; the substrate member 200, the spacermember 201 and the flexible membrane 202 defining a sealed cavity 203;wherein the flexible membrane 202 moves and/or deforms in response tointraocular pressure changes and the movement or deformation of theflexible membrane 202 is measured optically, wherein light from a lightsource 102, emitting one or more wavelengths of light eithersimultaneously or sequentially, is both transmitted and reflected by theflexible membrane 202, and reflected by the substrate member 200, andwherein the light reflected by the substrate member 200 interferes withlight reflected from the flexible membrane 202 to create an interferencepattern 300, the method includes the steps of: S1302 performing, by aprocessing device 107, a phase calculation on the interference pattern300 to determine phase angles of the interference pattern 300; and S1304correlating the phase angles with pressure.

An exemplary interference pattern 300 has intensity, I, that is periodicwith the square of the spatial variables. An exemplary signal of thistype is I(x,y)=A cos(k_(x)x²+k_(y)y²)+B where A is the amplitude of thefringe modulation, k_(x) and k_(y) are the spatial frequencies of therings in the x- and y-directions, x and y are the spatial coordinatesacross the sensor surface, and B is constant offset of zero light level.In practice, this signal may be discretely sampled by an electronicimaging device so that the pixel value at the j^(th),k^(th) location inthe image matrix is given by I_(jk)=A cos(k_(x)x_(j) ²+k_(y)y_(k) ²)+B.

To determine the phase of the interference pattern 300, thetwo-dimensional image is multiplied by a kernel of the formK(k_(x),k_(y),x,y)=exp[−ik_(x)x²−ik_(y)y²]. For each value of k_(x) andk_(y) the product of the signal and kernel is integrated over x and y toyield the integral transform given byF(k_(x),k_(y))=∫∫I(x,y)exp[−jk_(x)x²−jk_(y)y²]dxdy. FIG. 3B shows theabsolute value of the integral transform 302, |F(k_(x),k_(y))|. As canbe seen in FIG. 3B, there is a peak value 301 in |F(k_(x),k_(y))| at aparticular non-zero pair of values for k_(x) and k_(y). At this peakvalue 301, the phase angle of the transform,

${{\phi\left( {k_{x},k_{y}} \right)} = {{arc}\;{\tan\left( \frac{{Im}\left\{ {F\left( {k_{x},k_{y}} \right)} \right\}}{{Re}\left\{ {F\left( {k_{x},k_{y}} \right)} \right\}} \right)}}},$will relate to how the rings are spatially positioned. Because thespatial position of the rings in the interference pattern 300 is relatedto the deflection of the flexible membrane 202 with respect to thesubstrate member 200, one can determine intraocular pressure from thephase of the transform at the spatial frequencies corresponding to thepeak 301. A change in the phase of the transform indicates a shift inposition of the rings and thus a change in pressure. In an embodiment,the transform is computed discretely and becomes

${F\left( {k_{x},k_{y}} \right)} = {\sum\limits_{j = 0}^{N}{\sum\limits_{k = 0}^{M}{I_{jk}{\exp\left\lbrack {{{- {ik}_{x}}x_{j}^{2}} - {{ik}_{y}y_{k}^{2}}} \right\rbrack}}}}$where N is the number of pixels in the x-direction and M is the numberof pixels in the y-direction.

In an embodiment, the spatial frequencies are known and the transformneed only be computed for one value of k_(x) and one value of k_(y). Inan embodiment, the spatial frequencies are not known, and the integraltransform is computed for a range of spatial frequencies, the peak 301in the absolute value of the integral transform 302 is identified, andthe phase is computed at the spatial frequencies corresponding to thepeak 301.

FIG. 3C plots the phase at the peak 301 of |F(k_(x),k_(y))| as afunction of pressure for experimentally obtained data. The sensor wasplaced in a sealed chamber with water around it, and the pressure wasvaried with a syringe. The pressure values on the abscissa were measuredwith a commercial analog pressure sensor placed in the same test chamberas the optical sensor. It is apparent that phase is correlated withpressure, and that the sensor covers a range of physiologically relevantpressures found in the human eye (5-30 mmHg). In addition, this sensordesign covers this range of pressures relative to atmospheric pressurewithout exceeding a phase change of 2n and there is no ambiguity in thephase-pressure relationship.

In an embodiment, the normal axis of the intraocular pressure sensor 101is not required to be coincident with the optical axis of at least oneof the light source 102 and detector 106. The interference pattern 300is spatially compressed along the direction associated with the tiltangle of the sensor 101. For example, if the patient looks to the sideduring a pressure measurement, the sensor 101 will rotate about they-axis and the interference pattern 300 will appear to compress in thex-direction. Compression of the interference pattern 300 in space shiftsthe peak 301 in |F(k_(x),k_(y))| to a higher spatial frequency. Thus,one can determine the angle of the sensor 101 with respect to theoptical axis of the readout system from the values of k_(x) and k_(y).This allows one to correct for any error that would otherwise beintroduced by the patient not looking directly along the optical readoutaxis. FIG. 4A shows an interference pattern 300 with the sensor rotatedby 25 degrees about its y-axis. This rotation is extreme, but is usedfor exemplary purposes to make the fringe compression appear clear byvisual inspection. FIG. 4B shows the absolute value of the integraltransform 302, |F(k_(x),k_(y))|. In this case, the peak 301 shifts tohigher values of k_(x) because of the rotation.

In an embodiment, at least one of a larger range of pressures needs tobe measured or greater sensitivity, i.e. phase change with change inpressure, is required. Two wavelengths of light illuminate the sensor101. In an embodiment, the wavelengths illuminate the sensorsequentially so the interference pattern 300 from each wavelength ismeasured separately. FIG. 9A and FIG. 9B show two interference patterns300 for sequential measurement of a sensor with wavelengths of 700 nmand 900 nm respectively. FIG. 9C and FIG. 9D show the absolute value ofthe integral transforms 302 for 700 nm and 900 nm wavelengthsrespectively. The peak values 301 occur at different spatial frequenciesfor the two different wavelengths. Calculating the phase at the spatialfrequencies corresponding to each peak 301 in each transform allowunambiguous determination of the pressure even if the phase change ofone or both interference patterns 300 exceeds 2π.

In an embodiment, the two wavelengths illuminate the sensorsimultaneously, and a single interference pattern 300 is captured by thedetector 106. FIG. 10A shows the interference pattern 300 and FIG. 10Bshows the absolute value of its integral transform 302 when the sensoris simultaneously illuminated with wavelengths of 700 nm and 900 nm. Inthis case the two wavelengths result in a peak 1000 for 900 nm and apeak 1001 for 700 nm in a single integral transform. The shorterwavelength yields a higher spatial frequency. The two phases associatedwith the two wavelengths can be used to track phase changes larger than2n without ambiguity in the relationship between phase and pressure.This method can increase the dynamic range of a sensor or allow acertain dynamic range to be maintained while redesigning the sensor forgreater sensitivity.

Thus, the invention provides systems, devices, and methods for measuringintraocular pressure. One of ordinary skill in the art will recognizethat additional steps and configurations are possible without departingfrom the teachings of the invention. This detailed description, andparticularly the specific details of the exemplary embodiment disclosed,is given primarily for clearness of understanding and no unnecessarylimitations are to be understood therefrom, for modifications willbecome evident to those skilled in the art upon reading this disclosureand may be made without departing from the spirit or scope of theclaimed invention.

What is claimed is:
 1. A system for determination of intraocularpressure, the system comprising: an intraocular pressure sensorincluding a substrate member, a spacer member, and a flexible membrane,the substrate member, the spacer member and the flexible membraneforming walls of a sealed cavity having no openings for fluidcommunication with a vacuum, the flexible membrane having an exteriorsurface and being configured to deform in response to intraocularpressure when the intraocular pressure sensor is implanted in an eye; alight source configured to illuminate the exterior surface of theflexible membrane with an incident light including one or morewavelengths of light; the flexible membrane configured to partiallytransmit and partially reflect the incident light, the substrate memberconfigured to reflect the incident light that is partially transmittedback through the flexible membrane to create an interference patternwith the incident light that is partially reflected, the interferencepattern consisting of bright and dark rings having a separationdepending on a curvature of the flexible membrane; and an electronicimaging device configured to capture an image of the interferencepattern.
 2. The system of claim 1, further comprising a processingdevice in communication with the electronic imaging device, wherein theprocessing device performs a phase calculation on the image of theinterference pattern to determine phase angles of the interferencepattern, and correlates the phase angles with intraocular pressure. 3.The system of claim 2, wherein the processing device further performsthe phase calculation using an integral transform and calculates thephases at one or more spatial frequencies corresponding to peaks in anabsolute value of the integral transform.
 4. The system of claim 3,wherein the processing device uses the values of the spatial frequenciescorresponding to peaks in the absolute value of the integral transformto correct for errors which arise from angular deviation of a sensornormal from an optical axis of a readout system.
 5. The system of claim2, wherein each wavelength emitted by the light source has a coherencelength longer than the twice the separation between the flexiblemembrane and the substrate member.
 6. The system of claim 2, furthercomprising an optical filter positioned between the intraocular pressuresensor and at least one of the light source and the electronic imagingdevice, and providing an optical coherence length greater than twice thedistance from the flexible membrane to the substrate member.
 7. Thesystem of claim 2, wherein the light source is modulated in time toallow for lock-in detection of the interference pattern.
 8. The systemof claim 2, wherein the light source emits multiple wavelengths oflight, either simultaneously or sequentially, and wherein the dimensionsof the flexible membrane allow a phase change in the interferencepattern of greater than 2π for at least one of the multiple wavelengthsof light.
 9. The system of claim 1, further comprising an anchoringmember including an arm, the intraocular pressure sensor positioned onthe arm, and a second intraocular pressure sensor positioned on the armand having at least one of a different diameter, shape, membranethickness, membrane material, and substrate material, the intraocularpressure sensor and the second intraocular pressure sensor providing atleast one of redundant pressure measurement, failure detection,compensation for temperature fluctuations in the eye, increased pressuremeasurement sensitivity, and increased pressure measurement dynamicrange.
 10. The system of claim 1, further comprising an anchoring memberincluding an arm, the intraocular pressure sensor positioned on the arm,and a second intraocular pressure sensor positioned on the arm andconfigured to provide redundant pressure measurements that increaseconfidence in the pressure reported by the system and to serve as anindication of failure if one of the intraocular pressure sensor and thesecond intraocular pressure sensor fails.
 11. A device for measuringintraocular pressure comprising: an intraocular pressure sensorincluding a substrate member, a spacer member, and a flexible membrane,the substrate member, the spacer member and the flexible membraneforming walls of a sealed cavity having no openings for fluidcommunication with a vacuum, the flexible membrane having an exteriorsurface and being configured to deform in response to intraocularpressure-changes when the intraocular pressure sensor is implanted in aneye, the flexible membrane configured to partially transmit andpartially reflect an incident light that is incident on the exteriorsurface of the flexible membrane, the substrate member configured toreflect the incident light that is partially transmitted back throughthe flexible membrane to create an interference pattern with theincident light that is partially reflected, the interference patternconsisting of bright and dark rings corresponding to the intraocularpressure; an anchoring member attached to the intraocular pressuresensor for immobilizing the intraocular pressure sensor in the eye. 12.The device of claim 11, wherein the anchoring member comprises a platefor insertion in a scleral pocket and for immobilizing the device, andan arm for entering an anterior chamber of the eye through a scleraltunnel.
 13. The device of claim 12, wherein the plate includes holes forsuturing the plate to the eye.
 14. The device of claim 12, wherein theplate includes holes for assisting wound healing.
 15. The device ofclaim 11, wherein the anchoring member comprises a pair of pincers toenclavate an iris of the eye.
 16. The device of claim 11, wherein theanchoring member includes an arm, the intraocular pressure sensorpositioned on the arm, further comprising a second intraocular pressuresensor positioned on the arm and having at least one of a differentdiameter, shape, membrane thickness, membrane material, and substratematerial, the intraocular pressure sensor and the second intraocularpressure sensor providing at least one of redundant pressuremeasurement, failure detection, compensation for temperaturefluctuations in the eye, increased pressure measurement sensitivity, andincreased pressure measurement dynamic range.
 17. The device of claim11, wherein the anchoring member is formed from a biocompatible materialselected from a group consisting of polymethylmethacrylate, silicone,biocompatible metals, and biocompatible metal alloys.
 18. The device ofclaim 11, wherein the anchoring member includes an arm, the intraocularpressure sensor positioned on the arm, further comprising a secondintraocular pressure sensor positioned on the arm and configured toprovide redundant pressure measurements that increase confidence in thepressure reported by the system and to serve as an indication of failureif one of the intraocular pressure sensor and the second intraocularpressure sensor fails.
 19. The device of claim 11, further comprising aprotective member attached to the anchoring member and covering theintraocular pressure sensor to prevent contact between the flexiblemembrane and portions of the eye.
 20. The device of claim 19, whereinthe protective member is formed from a biocompatible material selectedfrom a group consisting of polymethylmethacrylate, silicone,biocompatible metals, and biocompatible metal alloys.